Metabolomic-based analysis reveals bile acid-mediated ovarian failure induced by low temperature in zebrafish

As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish(Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species,27℃, to lower temperatures of 22℃, 20℃, and 13℃ over a period of two weeks. Comparative metabolomic(six biological replicates for each temperature) and transcriptomic(four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production,antioxidant function, and lipid and protein catabolism.Disrupted reproductive hormones, increased proteolysis,and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.

Current Status of Stem Cells in the Treatment of Premature Ovarian Failure

Premature ovarian failure (POF) is a prevalent cause of female infertility. POF features include estrogen hypofunction, amenorrhea, infertility, and high gonadotropin levels. The etiology of POF is genetic diseases, autoimmune diseases, enzyme defects and environmental factors. The development of Regenerative medicine has made stem cell and exosome (EXOs) therapy effective for POF. This review discusses POF stem cell research and development.

Mechanism of Camellia nitidissima Chi in Treating Premature Ovarian Failure Based on Network Pharmacology and Molecular Docking

[Objectives]This study was conducted to explore active components and molecular biological mechanisms of Camellia nitidissima Chi in the treatment of premature ovarian failure(POF).[Methods]The active components and corresponding targets of C.nitidissima Chi were retrieved through literature and the TCMSP database.POF-related disease targets were identified using the OMIM and Genecards databases.A PPI network was constructed using the STRING database and Cytoscape 3.10.2.A herb-active component-target-pathway network diagram was also constructed with Cytoscape 3.10.2.The CytoNCA plugin was used to screen out the top five core targets and core active components.GO and KEGG enrichment analyses of the intersecting targets were performed using DAVID.Finally,molecular docking was conducted using Auto Dock to verify the interaction between core targets and active components,and visualization was done using PyMol.[Results]A total of 26 active components and 461 targets of C.nitidissima Chi were identified,with 154 intersecting targets related to POF.The core components of the herb included 1,1'-bi-2-naphthol,3',4-O-dimethylcedrusin,eriodictyol,quercetin,and vanillin.The PPI network revealed that the main targets were epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),proto-oncogene Src(SRC),hypoxia-inducible factor 1α(HIF1A),and estrogen receptor 1(ESR1).KEGG enrichment analysis revealed 10 pathways closely related to POF,mainly involving the PI3K-Akt signaling pathway,chemical carcinogenesis-reactive oxygen species,endocrine resistance,and the HIF-1 signaling pathway.Molecular docking results showed that the core active components had strong binding activity with the targets.[Conclusions]C.nitidissima Chi has multi-component,multi-target,and multi-pathway characteristics in the comprehensive treatment of POF,providing informational support for its clinical application.

Recent Research Progress in Premature Ovarian Failure

Premature ovarian failure refers to ovarian function failure in women before the age of 40 years due to follicular depletion or follicular dysfunction resulting in abnormal hormone levels.The etiology and pathogenesis of premature ovarian failure may be related to genetic,immunological,medical,environmental,infectious,psychological and enzyme deficiencies.The treatment involves Western medicine,Chinese medicine,and a combination of Chinese and Western medicine,and the treatment level includes hormone level,cellular level,surgery and psychological aspect.This paper would like to review the progress of the etiology,pathogenesis and treatment of premature ovarian failure in recent years.

Study on the mechanism of effect of Daodi Tongguan Decoction on rats with premature ovarian failure

Objective:To investigate the mechanism of the effect of Daodi Tongguan Decoction on ovarian function in rats with premature ovarian failure.Methods:Forty SD female rats with regular estrous cycle were randomly divided into the blank group,the model group,the positive group(Bujiale 0.099 mg/kg),the Daodigitongguan decoction high-dose group(1.4 g/100 g)and the Daodigitongguan decoction medium-dose group(0.7 g/100 g).The model group,positive group,Daodi Tongguan Decoction high-dose group and Daodi Tongguan decoction medium-dose group were given Tripterygium wilfordii polyglycoside tablets suspension(50 mg/kg)by continuous gavage for 14 days to establish a rat model of premature ovarian failure.After the modeling,each group was given the corresponding intervention agent for 28 consecutive days.After the intervention,serum and ovarian tissue were collected from rats in each group.The morphological structure of rat ovarian tissue was observed after HE staining.Serum AMH level was determined by ELISA.The expressions of Bcl-2,Bax and VEGF in ovarian tissue were detected by IHC.The apoptosis of granulosa cells in ovary was observed by TUNEL.Results:Compared to the normal group,the growth follicles in the model group were reduced and the atretic follicles were increased.Serum AMH level was significantly decreased(P<0.01).The expression of Bax protein in ovarian tissue was increased(P<0.01).The protein expressions of Bcl-2 and VEGF were decreased(P<0.01,P<0.05),and the apoptosis rate of follicular granulosa cells in ovarian tissue was increased(P<0.01).Compared to the molding group,the serum AMH level in the TCM dose groups was increased to varying degrees,and the change of the AMH in high-dose group was the most significant(P<0.05).The expression of Bax protein in ovarian tissue decreased(P<0.05),while the expression of Bcl-2 and VEGF protein increased(P<0.05,P<0.05).The apoptosis rate of follicular granulosa cells in ovarian tissue was decreased in the high dose group(P<0.05).Conclusion:Daodi Tongguan Decoction can improve the histological morphology of ovary and relieve ovarian injury,and its mechanism may be related to improving the sex hormone level of POF model rats,reducing the expression level of Bax protein in ovarian tissue,increasing the expression level of Bcl-2 and VEGF protein in ovarian tissue,and reducing the apoptosis rate of follicular granulosa cells in ovarian tissue.

Intermittent spontaneous ovulation in patients with premature ovarian failure:Three case reports and review of literature

BACKGROUND Premature ovarian failure(POF)is the end-stage of a decline in ovarian function prior to the age of 40 years that involves symptoms associated with low estradiol(E2)levels and a minimal probability of pregnancy.This increases the physical and psychological burden experienced by young women of reproductive age,particularly with regards to over-diagnosis.CASE SUMMARY Here,we report three cases(29,22,and 33 years-of-age)diagnosed with POF after experiencing secondary amenorrhea for more than one year,serum levels of follicle-stimulating hormone(FSH)>40 IU/L on two occasions with an interval of more than 4 wk,and negative progesterone withdrawal tests.All three patients were intermittently administered with drugs to create an artificial cycle.During the subsequent discontinuation period,the patients experienced intermittent follicular growth and spontaneous ovulation.One patient experienced two natural pregnancies(both with embryo arrest).CONCLUSION Our findings suggest that young patients with POF can experience unpredictable and intermittent spontaneous follicular development,ovulation,and even natural pregnancy.Clinicians should provide appropriate medical guidance and individualized treatments according to fertility requirements,genetic risks and hypoestrogenic symptoms as soon as possible.

Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure

BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone marrow,umbilical cord,peripheral blood and amniotic fluid can migrate and proliferate to the ovary,promote ovarian function repair,increase the number of follicles and granulosa cells at all levels of ovary,improve endocrine function,and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.AIM To study the ability of human umbilical cord mesenchymal stem cells(hUCMSCs)to repair ovarian injury after chemotherapy.METHODS A total of 110 female BALB/c mice(aged 7-8 wk old)with body masses of 16.0-20.0 g were selected.The mice were fed until 12 wk of age,and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice.Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight:model group,positive control group and hUCMSC group,and each group had 25 mice.Another 25 mice were used as negative controls.The mice in the hUCMSC group were injected with hUCMSCs in the tail vein,and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein.On the 1^st,15^th,30^th,45^th,and 60^th days after intravenous administration,vaginal smears were made to monitor the estrous cycles of the mice.The ovaries were weighed,and pathological sections were made to observe the morphology of the follicles;blood samples were collected to monitor the concentration of sex hormones(oestradiol and follicle-stimulating hormone).RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment.Mice in the hUCMSC group and the positive control group resumed normal estrous cycles.The ovarian weight of the model group mice continued to decline.The ovarian weight of the hUCMSC group mice and the positive control group mice decreased first and then gradually increased,and the ovarian weight of the hUCMSC group mice was heavier than that of the positive control group mice.The difference was statistically significant(P<0.05).Compared with the negative control group,the model group experienced a decrease in oestradiol and an increase in follicle-stimulating hormone,and the difference was statistically significant(P<0.05).Compared with the model group,the hUCMSC and positive control groups experienced a slight increase in oestradiol and a decrease in follicle-stimulating hormone;the difference was statistically significant(P<0.05).The pathological examination revealed that the mouse ovaries from the model group were atrophied,the volume was reduced,the cortical and medullary structures were disordered,the number of follicles at all stages was significantly reduced,the number of atretic follicles increased,the number of primordial follicles and corpus luteum significantly decreased,and the corpus luteum had an irregular shape.Compared with those of the model group,the lesions of the hUCMSC and positive control groups significantly improved.CONCLUSION hUCMSCs can repair ovarian tissue damaged by chemotherapy to a certain extent,can improve the degree of apoptosis in ovarian tissue,and can improve the endocrine function of mouse ovaries.

Premature ovarian failure and oocyte donation──a report of 30 cases

Objective: To study oocyte donation in treatment of premature ovarian failure.Methods:Thirty premature ovarian failure patients receiving hormone replacement therapy had un-dergone 54 treatment cycles of in vitro fertilization with their husbands’ sperm and donors’ oocytes.Ovulation induction was achieved by GnRH-α/HMG/hCG regimen in donors. Embryos transfers were performed in recipients from 15th to 20th day of hormone replacement therapy cycle. Preclinical preg-nancies were defined when serum β-hCG performed on day 14 post embryo transfer >3. 1ng/ml. Clini-cal pregnancies was diagnosed by the presence of a gestation sac with transvaginal ultrasound at six weeks of gestation.Results:Clinical pregnancy rate per embryo transfer cycle was 35- 2% (19/54). The first baby was deliveried on Jan 14, 1994 in premature ovarian failure patient with hormone replacement therapy and oocyte donation in China. Comharison of the results showed a singnificant increase in number of em-bryos transfer, embryo scoring and clinical pregnancy rate (54. 2 % ) in the whole cohort where oocytes were used. The P value was <0.05, <0. 001, <0.05 respectively. However the spontaneous abortion rate(15. 4% ) significantly decreased (P<0.001 ). No difference was found in the embryos scoring and the number of embryos transfer between groups with age less than 3O years or more than 30 years. But clinical pregnancy rate in the younger group (42. 9% ) was significantly higher than in the older group (30. 3%). The endometrium receptivity window of a 2-days embryo was from 15th to 19th day of a 28 days cycle. The highest pregnancy rate was in day 16 to 18 in the 28 days cycle.Conclusion: Hormone replacement therapy and oocyte donation is a effective method of obtaining successful pregnancy for those with premature ovarian failure. The quality of oocyte is an important factor that affects the pregnancy rate and spontaneous abortion rate. The endometrium receptivity ia al-so a major factor affecting the pregnancy rate, which declined with increasing age.

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure

BACKGROUND Premature ovarian failure(POF)affects many adult women less than 40 years of age and leads to infertility.According to previous reports,various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF.Human embryonic stem cells(ES)provide an alternative source for mesenchymal stem cells(MSCs)because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics.Embryonic stem cell-derived mesenchymal stem cells(ES-MSCs)are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs.However,possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated.AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells(BMMSCs)in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure.METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF.Either human ES-MSCs or BMMSCs were transplanted into these mice.Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ESMSCs and/or BM-MSCs,we evaluated body weight,estrous cyclicity,folliclestimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation.Moreover,terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling,real-time PCR,Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation.Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor,insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function.RESULTS The human ES-MSCs significantly restored hormone secretion,survival rate and reproductive function in POF mice,which was similar to the results obtained with BM-MSCs.Gene expression analysis and the terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling assay results indicated that the ES-MSCs and/or BM-MSCs reduced apoptosis in the follicles.Notably,the transplanted mice generated new offspring.The results of different analyses showed increases in antiapoptotic and trophic proteins and genes.CONCLUSION These results suggested that transplantation of human ES-MSCs were similar to BM-MSCs in that they could restore the structure of the injured ovarian tissue and its function in chemotherapy-induced damaged POF mice and rescue fertility.The possible mechanisms of human ES-MSC were related to promotion of follicular development,ovarian secretion,fertility via a paracrine effect and ovarian cell survival.

Analysis of anti-zona pellucida antibody and tumor necrosis factor-α,γ-interferon and interleukin-2 in sera from patients with premature ovarian failure

Objective:To investigate the role and the clinical significance of anti-zona pellucidaantibody (AzpAb) and tumor necrosis factor-α(TNF-α),γ-interferon(IFN-γ) and inter-leukin-2 (IL-2) in sera from patients with premature ovarian failure (POF).Methods: The AzpAb in the serum of POF patient was analyzed by means ofELISA. The levels of TNF-α, IL-2 and IFN-γ in the serum were determined by meansof radioimmunoassay (RIA).Results:The level of serum AzpAb in the POF patients was significantly higher thanthat of the normal controls(P＜0.001). The levels of TNF-α and IL-2 were significantlyreduced (P＜0. 001), and the level of IFN-γ was significantly elevated (P＜0.01). Thelevels of above three cytokines in AzpAb positive group were significantly higher thanthose of the negative group in POF patients.Conclusion: This study suggested that AzpAb, TNF-α, IFN-γ and IL-2 might playimportant roles in the pathogenesis of autoimmune POF.

Infertility and ovarian failure in celiac disease

Unexplained infertility in females may be a devastating event for the reproductive-aged female.However,infertility may be due to ovarian failure associated with celiac disease,an immune-mediated disorder that may have few or no symptoms and can be successfully treated.In some prospective serologically-based studies,over 4% of infertile females may prove to have celiac disease.Serological screening for celiac disease is relatively inexpensive and involves testing for antibodiesto tissue transglutaminase.If positive,a small intestinal biopsy should be done to confirm the diagnosis.The initial treatment for this disorder is a gluten-free diet.To date,a number of reports have indicated that this treatment for celiac disease may result in successful pregnancy,in spite of prolonged periods of infertility.Celiac disease,when untreated,may also lead to several adverse events following pregnancy including increased risk of recurrent abortions,low birthweight and impaired fetal growth.Recent molecular and pathological studies from different laboratories suggest that altered placental function may be due to binding to cells in the trophoblast by tissue transglutaminase antibodies impairing embryo implantation and leading to failure of early pregnancy or retarded intrauterine growth.

Auricular acupoint application combined with Fujing prescription treatment for patients with premature ovarian failure

Background:To study the efficacy of Fujing prescription combined with auricular acupoint application in premature ovarian failure and its effect on hormone levels.Methods:From March 2018 to March 2020,100 patients with premature ovarian failure treated in our outpatient clinic were selected and randomly divided into a control group of 50 cases and a treatment group of 50 cases.The control group was treated with Femoston for 28 consecutive days,and the treatment group was treated with not only Femoston,but also Fujing prescription and auricular acupoint application.The patients in the two groups were treated with a 3-month course of treatment.The clinical efficacy,traditional Chinese medicine integral,serum hormone level,immune index and the occurrence of adverse reactions were compared between the two groups.Results:After treatment,the indexes of IgG,IgM and IgA in the treatment group were all increased(P<0.05 for all);compared with the control group,the incidence of adverse reactions in the treatment group was lower(P<0.05).Conclusion:The combination of Fujing prescription and auricular acupoint application in the treatment of premature ovarian failure can improve patients'clinical symptoms significantly,resulting in a decrease in follicle-stimulating hormone levels and an increase in estrogen levels.The combination of Fujing prescription and acupoint application has provided a clinical basis for the TCM treatment of premature ovarian failure.

A Preliminary Study on the Mechanism of Premature Ovarian Failure

Premature ovarian failure(POF)refers to the failure of ovaries which causes amenorrhea before the age of 40.It is characterized by primary or secondary amenorrhea along with elevated blood gonadotropin levels and decreased estrogen levels with varying degrees of low estrogen symptoms such as hot flashes and sweating,facial flushing,reduced libido,and so on.Premature ovarian failure(POF)is a common endocrine disease in gynecology.The incidence of POF is increasing year by year and the affected population increasingly involves the younger-aged groups.Its etiology is complex and diverse involving many factors such as genetics,immunity,medical treatment,environment endocrine disruptors,etc.It is also affected by long-term smoking,alcohol intake,and other behaviors which damage patients9 physical and mental health.In recent years,the effects of gene therapy in restoring ovarian function and improving fertility in animal experiments have provided a new direction for POF patients.This article discusses the etiology and possible pathogenesis of POF and BRCA from various aspects as well as summarizes the recent research status and progress of new treatment methods of POF.

Effect and Mechanism of Bushen Huoxue Recipe on Ovarian Reserve in Mice with Premature Ovarian Failure

The aim of the present study was to explore the effect and mechanism of Bushen Huoxue recipe（BHR） on ovarian reserve in mice with premature ovarian failure（POF）. Mice were divided into 3 groups： normal group, model group and BHR group. Intraperitoneal injection of cyclophosphamide was performed to create the POF model. Primordial follicular（PDF） number, ovarian wet weight, ovarian index, and estrous cycle were analyzed to evaluate the effect of BHR on POF. Meanwhile, the m RNA and protein level of Mouse Vasa Homologue（MVH） in the bone marrow, peripheral blood and ovary were detected, to explore the underlying mechanism of the treatment efficacy of BHR on ovarian reserve. By the time of BHR treatment for 28 days, BHR increased the PDF number and shortened the estrous cycle of POF mice. BHR also decreased the m RNA level of MVH in the bone marrow, and increased m RNA and protein level of MVH in the ovary of POF mice. Our results demonstrated a treatment efficacy of BHR on POF mice, and revealed that BHR might repair the dysfunction of germline stem cells in the bone marrow, and thus to improve the ovarian reserve and enhance the ovarian function of POF mice through neo-oogenesis.

Distribution of CD 4^+ Lym phocyte Th1/Th2 Subsets in Peripheral Blood of Women with Idiopathic Prem ature Ovarian Failure

Thepathogenesisof prem ature ovarian failure (POF) rem ains unknow n. Accu- m ulated evidences indicate that abnorm ality in the im m une system m ay be one of the m ajor reasonsand theim balanceof Thelp typeI(Th1) and Thelp typeII(Th2) m ay play an importantrolein theprocess. Study of thedistribution and functionalstatusof Th1/Th2 m ay behelpfulforevaluating thepathogenesisof POF.13 patientsw ith id- iopathic POFand 7 w om en of reproductiveagew ith norm alcyclew ereenrolled in this study.The percentage of Th1 and Th2 cellsfrom peripheralblood of thepatientsand the controls w as studied using FITC labelled CD4 m Ab to separate CD4+ cells by FACS, in com bination w ith in situ hybridization using Dig-labelled IL2, IL6 cDNA probes.Results:The patients w ith POF had significantly higher percentage of Th1 cellsascompared w ith the controls(49.76±9.22,20.06±7.10respectively, P< 0.001).The ratio of Th1/Th2 in thepatientsw ith POFw assignificantly higherthan thatof thecontrols(1.15±0.17, 0.63±0.09, P< 0.001). Conclusions: Thefindings of thisstudy suggestthatpatientsw ith POFhaveincreased Th1 cellactivation, w hich m ay be related to the pathogenesisof POF. Corresponding author: WANG Yi-li E-m ail: w yl@ irix. xam u. edu. cn

Beneficial Effects of Tibolone on Sexual Dys-function in Women with Premature Ovarian Failure (POF)

Introduction: Premature Ovarian Failure (POF) is cessation of ovarian functions before the age of 40 years old with consequent cessation of menstruation. Objective of study: The aim of this study was to evaluate the association between Premature Ovarian Failure and sexual dysfunctions and outcome of management with tibolone. Patients and Methods: Thirty-one women with Premature Ovarian Failure seen at the outpatient clinic of Maternity Hospital were enrolled into the study with 31 healthy women as control group. The instrument of data collection included two types of questionnaires to assess the effect of Premature Ovarian Failure on sexuality. All the women with POF had oral tibolone 2.5 mg for at least one year and the second questionnaire and the profiles were repeated. Results: Of the 31 women with POF that presented with sexual dysfunction (SD), 27 (87.1%) complained of one or more SD domains such as reduced frequency of coitus, dyspareunia, vaginal dryness, reduced libido and general sexual satisfaction (P < 0.01), amenorrhea (P < 0.01) and hot flashes compared to 5 (16.1%) control women (P < 0.01). Administration of tibolone was associated with significant increase in frequency of coitus, reduced dyspareunia and vaginal dryness, increase libido and general satisfaction and happiness. Reduction of sexual dysfunction was predicated on the estrogenic, progestogenic and androgenic metabolite of tibolone through the reduction of serum level of FSH and LH and increased levels of estrogen and testosterone (P < 0.01). Tibolone had no adverse effect on serum lipid profile. Conclusion: Premature Ovarian Failure is associated with sexual dysfunction. Tibolone provides an effective means of treating sexual dysfunction caused by Premature Ovarian Failure.

Emotional Impacts of Premature Ovarian Failure in Kuwait

Premature Ovarian Failure (POF) is cessation of ovarian functions before the age of 40 years with consequent cessation of menstruation. The objective of study was therefore to evaluate the emotional reaction and self-efficacy of women with POF. Forty-two women confirmed to have Premature Ovarian Failure seen at the outpatient clinic of Maternity Hospital fulfilled the study criteria, were enrolled into the study. Another group of 42 healthy women formed the control group. The instrument of data collection included three types of questionnaires to assess the depth of emotional reaction to the diagnosis of POF including the subjects’ biodata, modified Health Orientation Scale (HOS) and Stanford Chronic Disease Self-Efficacy Scale. The women with POF presented at the clinic with infertility (P P P < 0.05). The diagnosis of ovarian insufficiency was a traumatic life event similar to bereavement (grieving of no obvious loss to others), with high level of anxiety, depression, fear of divorce, lower life satisfaction and impaired self-esteem. Fertility was generally of profound concern to all of them, because fertility was a societal landmark of womanhood and youth. The Stanford Chronic Self Efficacy scores were generally low (below 7) in coping with emotion reaction to loss of fertility, loss of menstruation, loss of self-esteem and other significant emotional reactions. The present study has demonstrated that Premature Ovarian Failure is associated with severe emotional distress and impaired ability to cope with them especially low self-esteem. A multidisciplinary management team is advocated for POF.

Effect of<i>Mentha longifolia</i>on FSH Serum Level in Premature Ovarian Failure

Purpose: Premature ovarian failure (POF) includes cessation of normal ovarian function before age 40, causing amenorrhea, menopausal symptoms and general health problems. Hormone replacement therapy (HRT) can be administered in order to prevent menopausal symptoms, osteoporosis and vascular complications. Due to the contraindications and side effects of HRT and the increasing demand for alternative therapeutic modalities, we used Mentha longifolia, which is known in the Iranian traditional medicine (ITM), as being able to cause menstrual bleeding in women with early amenorrhea and decreased FSH serum. Methods: In this pilot study, we report twenty seven amenorrheic women with POF who were referred to the Iranian traditional medicine clinic in Tehran and treated by Mentha longifolia. All those patients had high FSH levels and amenorrhea. They were in their fertility age, between 30 to 40 years old. They were asked to take a cup of herbal tea which was steeped with Mentha longifolia tea three times a day for 2 weeks in 3 menstural cycles. If the patients developed menstruation, the FSH serum level was measured immediately;otherwise they had an FSH measurement one month after the beginning of therapy. Results: Mean age of patients was 36.44 ± 1.5 years. Mean FSH level before treatment was 79.13 ± 19.17 mIU/ml, and after treatment was 27.83 ± 16.14 mIU/ml. In four patients who did not have any response, mean range of FSH was 82.37 ± 19.75 mIU/ml before treatment and afterwards it was 81.97 ± 21.52 mIU/ml. After treatment with herbal teas, there was a significant decrease in FSH (79.39 ± 19.17 to 27.83 ± 16.14 mIU/ml, p value < 0.001). All patient except four (14.81%) had mensturation after taking the herbal medicine. Those four patients showed no decrease in FSH level. More of the patients who used medicinal tea achieved regular monthly bleeding when followed for three cycles.

Bilateral Mixed Germ Cell Tumour in an Adolescent Girl with Premature Ovarian Failure

Germ cell tumours (GCTs) of the ovary are rare, comprising approximately 20% of all ovarian tumors with the malignant variant accounting for less than 5% of all ovarian neoplasms. Malignant mixed germ cell tumours are rarer still with dysgerminoma & yolk sac tumour being the most common components with three component variants being categorised in the rarest of rare varieties. Bilateral dysgerminomas occur in 15% of germ cell neoplasms but rarely present with premature ovarian failure. We present the case of an adolescent girl with a short history of abdominal pain and distension with amenorrhoea for a year. Clinical and radio ogical examination revealed a pelvic/adnexal mass with elevation of tumour markers and she had to undergo a staging laparotomy with bilateral salpingo-oophorectomy. Histopatholgy examination was reported as malignant mixed germ cell tumour of left ovary, predominantly with immature teratoma and minor components of yolk-sac tumour and dysgerminoma and right ovary with dysgerminoma. In view of mixed germ cell disease, she was planned for adjuvant chemotherapy.

Discussion on the mechanism of Erxian Decoction in the treatment of premature ovarian failure based on network pharmacology and molecular docking

Objective:To explore the mechanism of Erxian Decoction in the treatment of premature ovarian failure.Methods:Based on the method of network pharmacology and molecular docking,the active ingredients of each drug in Erxian Decoction were obtained by searching the TCMSP database;the premature ovarian failure disease targets were collected from the GeneCards,OMIM,PharmGkb and Drugbank databases,and the active ingredients and the disease gene targets were collected Click the intersection to get the predictive target of Erxian Decoction for the treatment of premature ovarian failure.Use Cytoscape 3.8.0 to construct a"drug-component-target-disease"network;construct a protein interaction network(PPI)and streamline the core network through STRING database and Cytoscape;use R Studio software to enrich the Erxiantang treatment POF with GO And KEGG pathway enrichment analysis.Use molecular docking technology to verify the results of the"drug-component-target-disease"network.Results:68 main active ingredients were screened,involving 182 gene targets,among which the main active ingredients include Quercetin,Luteolin,Kaempferol,etc.;The core target genes include RB1,TP53,FOS,CDKN1A,ESR1,AKT1,MAPK1,TNF,etc.;GO enrichment items were obtained,including the 2545 Biological Process(BP),89 Cellular Component(CC),212 Molecular Function(MF);KEGG pathways,including PI3K-Akt signaling pathway,MAPK signaling pathway,and AGE-RAGE signaling pathway in diabetic complications.The verification of the molecular docking results indicated that the main active ingredient has a good binding activity with the core target.Conclusion:This study preliminarily revealed that Erxian Decoction may play a role in the treatment of POF through multi-component,multi-target,and multi-channel synergy,which provides a reference for the next in-depth research.